HA-decorated nanoparticles as tumour-targeting nucleic acids carriers

摘要

In the context of nucleic acids delivery, an ideal carrier should not only provide the means for the transport of such payloads, but also protect their activity by limiting their exposure to harmful agents leading to either physical or enzymatic degradation. We here report on the development of nanoparticles designed to target CD44; which is a membrane protein overexpressed in many tumours, while also being the major receptor of hyaluronic acid (HA). The herein described particles present a chitosan (CS) core for nucleic acids complexation and a surface rich in HA. Nanoparticles CD44-HA mediated endocytic process, and the intracellular localisation of nucleic acids and their effects were observed using fluorescently labeled nanoparticle components. Sections and 3D reconstructions of the target (HT-29, colorectal cancer cells) and off-target (THP-1 macrophages) CD44-expressing cells were registered at different time points.